LICR NewsLink

December 2003

The James R. Kerr Program in China

In the mid 1990s, upon Dr. Old’s recommendation, the LICR Board of Directors established the James R. Kerr Program to expand LICR interactions with countries such as Russia and China that are scientifically talented but have had limited opportunities for international collaboration in areas of cancer research. The Program has steadily grown and matured under Dr. Old’s stewardship, to the point where it was appropriate for a Director to be appointed in September 2002.

A first interactive visit of this new phase of the Program was undertaken between October 18th and 24th, 2003, to one of the principle areas of interest of the Program, China. In addition to Dr. Andrew Simpson (Director of the James R. Kerr Program), Drs. Xin Lu (St. Mary’s Branch) and Achim Jungbluth (New York Branch) participated in the visit. Dr. Lu has now been appointed Associate Director of the Program with special responsibilities for China. Dr. Jungbluth coordinates the immunohistochemistry and tumor typing work at the New York Branch, a point of growing collaboration with the Chinese laboratories.

Following a one day lay-over in Beijing, the visiting group spent October 19th to 22nd in Xi’an at the laboratory of Dr. Bo-Quan Jin, Professor at the Department of Immunology at the Fourth Military Medical University where they were formally greeted by General Su Bo the President of the University. Dr. Jin and his colleagues have established a strong expertise in the generation of monoclonal antibodies (mAbs) and collaborate with the Institute by producing antibodies to proteins submitted by Branch members and affiliates (refer September 2003 NewsLink). This program is of increasing importance and immense potential and represents an excellent example of how researchers in the James R. Kerr Program and those in the Institute’s Branches can combine their efforts and talents to telling effect. An updated list of the antigens has been posted, and progress towards the generation of antibodies will be posted shortly, on the Intranet website.

As a result of the discussions that took place between the visiting group and the host scientists, led by Dr. Jin, a number of initiatives were decided in relation to the program. Firstly, with a view to increasing the rate of submission of antigens to Xi’an, it was decided that all individual researchers should send their material directly to China rather than first sending these to Dr. Lu in London. Again, detailed instructions for this will be posted soon on the Intranet site. This procedure will require more work on the part of the submitting investigator but should considerably shorten the turn around time by avoiding the delays inherent in accumulating batches of antigens to be sent from London. Additionally, since several of those involved in the monoclonal antibody generation in the Xi’an laboratory are undertaking post-graduate degrees, there is a very keen interest on their part to receive academic recognition for their contributions, therefore we recommend that our colleagues in Xi’an be included as authors on the first paper that describes the utilization of the monoclonal antibodies.

A second alteration is that the Xi’an laboratory will also undertake immunizations using DNA rather than protein. This is a more challenging strategy that is appropriate where antibodies to recombinant proteins have proven to be unsatisfactory or where the expression of the protein at all is extremely difficult. The laboratory already has experience with this, although they find it less consistent than protein vaccination. Obviously thought has to be put into the provision of suitable antigen for screening and supplied together with the plasmid construct. Investigators interested in pursing this route should contact Dr. Jin to discuss these details.

Lastly, the scientists in Xi’an wish to be actively involved in research utilizing the monoclonal antibodies generated. To this end, Dr. Jungbluth is now leading a collaboration with members of the Xi’an laboratory whereby they will be undertaking immunohistochemical analysis of normal tissue and the tumor distribution of new cancer-testis antigens against which monoclonal antibodies are being prepared.

The success that has been achieved is due to the work undertaken not only by Dr. Jin and his colleagues in China but also Drs. Lu and Paul Farrell at the LICR London St Mary’s Branch who have taken the responsibility for much of the interaction, and also Dr. Monique Zahn and her colleagues at the LICR Office of Information Technology (Lausanne) who prepare and update the intranet site. We trust that as we move forward the project will continue to grow in stature and contribution.

Following the visit to Xi’an, the group then spent the 22nd to the 24th in Beijing, principally to visit the laboratory of Dr. Wei-Feng Chen, Professor at the Department of Immunology of the Health Science Department of Peking University. Dr. Chen presented to the visitors a detailed report of the accomplishments of his group in the area of novel cancer-testis antigen identification, the expression of known cancer-testis antigens in hepatocellular carcinomas, the immune response to these antigens and the preparations for the execution of a Phase I clinical trial using NY-ESO-1. These investigations being undertaken in the Beijing laboratory have led to a number of publications in international journals. For the identification of novel cancer-testis antigens expressed in hepatocellular carcinomas, close collaboration will now be initiated with the New York Branch where candidates are being generated through analysis of high throughput sequencing technologies. These putative candidates will be validated in China using the material from hepatocellular tumors. The extensive contributions from this laboratory have placed hepatocellular carcinoma within the range of tumors covered by the cancer vaccine program and the clinical trial being planned will not only be the first undertaken within the James R. Kerr Program but also the first clinical trial in China being sponsored by a not-for-profit international institution.

The visiting group had the opportunity to discuss the issues involved with regulatory approval of this trial and its relevance to ongoing research in cancer immunotherapy in China with Professor Han, Vice-President, Standing Committee, Chinese People's Congress and President, Peking University Health Science Centre. In addition, the group had the opportunity to spend a morning at the Peking University Hepatology Institute People’s Hospital where the clinical trials will be undertaken, to see both the extensive clinical facilities and support laboratories that will be utilized.

The visiting group also had the opportunity to visit the Beijing Cancer Hospital where Dr. Yu Wang, a collaborator of the Cancer Vaccine Program and a recipient of a grant from the Cancer Research Institute (see accompanying article on the Cancer Vaccine Program), is establishing her cancer vaccine monitoring laboratory. The group was treated to an overview of the extensive research program being undertaken in the hospital, visited the excellently appointed research laboratories of Dr. Wang and had the opportunity to meet with Dr. Wei-Cheng You, Director of the Hospital. It is clear that at this hospital, extensive opportunities also exist for the study of cancer immunology and for the eventual establishment of clinical trials.

The entire visiting group is profoundly grateful to the extremely kind hospitality that we received from all our hosts and very much enjoyed this wonderful visit to our colleagues in China. The work being undertaken exemplifies the contributions to the Institute being made by the James R. Kerr Program, as envisioned by Dr. Old at its inception. It encompasses both collaborative interactions with the highest level of scientific talent and expertise and also access to regional variations in the set of diseases we study.

Andrew Simpson, Director, James R. Kerr Program
November 11, 2003